期刊
FREE RADICAL RESEARCH
卷 51, 期 7-8, 页码 669-683出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715762.2017.1361532
关键词
Astragaloside IV; cisplatin; acute kidney injury (AKI); KIM-1; Nrf2
资金
- Hong Kong, Macao, and Taiwan Science & Technology Cooperation Program of China [2014DFT30090]
- National Natural Science Foundation of China [81373865, 81573748]
- Science and Technology Commission of Shanghai Municipality [14140903200]
- Program of Shanghai Academic Research Leader [16XD1401900]
Nephrotoxicity remains a serious adverse effect of cisplatin chemotherapy, limiting its clinical usage. Numerous studies show that oxidative stress and inflammation are closely associated with cisplatin-induced renal damage. Astragaloside IV (AS-IV) has been found to possess antioxidant and anti-inflammation functions. Therefore, we investigated the potential curative effects of AS-IV against cisplatin-induced renal injury and the possible cellular mechanism for activity, both in vitro and in vivo. We found that pretreatment of HK-2 cells with AS-IV could mitigate cisplatin-induced cell damage caused by oxygen-free radicals and the inflammatory response, as evidenced by reduced formation of reactive oxygen species (ROS) and inflammatory cytokines. AS-IV improved cisplatin-induced renal dysfunction and histopathological injury in mice. Additionally, AS-IV enhanced the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). It also inhibited cisplatin-induced overproduction of kidney injury molecule-1 (KIM-1), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF alpha), and interleukin-1 beta (IL-1 beta) in kidney tissues. We found that the protective effects of AS-IV occurred via activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins and inhibition of nuclear factor-kappa ppaB (NF-kappa B) activation. Further, small interfering RNA (siRNA) knockdown of Nrf2 abrogated the protective effects of AS-IV against cisplatin-induced oxidative stress and blocked the inhibitory effects of AS-IV on cisplatin-induced NF-kappa B activation and inflammatory cytokine production. In conclusion, our data suggested that AS-IV attenuated cisplatin-mediated renal injury, and these protective effects might be due to inhibition of both oxidative damage and inflammatory response via activation of Nrf2 system and suppression of NF-kappa B activation.
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